Effect of Fentanyl Addition to Local Anaesthetic in Peribulbar Block

divided into two groups randomly, each of them with 20 patients. In Control group patients received local anaesthetic only ,while Fentanyl group receive 20 mcg fentanyl added to local anaesthetic, the onset and duration of lid and globe akinesia were assessed at 1,3,5,and 10 min. Postoperative VAS was recorded each hour up to 6 th hour. The results show statistically significant difference between the two groups in the onset of lid akinesia. Fentanyl group had faster onset of lid akinesia and had significantly longer duration of akinesia (196.5 ± 14.24 min).There is statistically significant difference between the two groups in the onset of globe akinesia at 3, 5 min. Fentanyl group had faster onset than Control group and had longer duration of globe akinesia (294 ± 17.89 min). Fentanyl group had prolonged duration of analgesia 3.25+ 0.67 hr as compared to 1.85+ 0.67 in Control group, P =0.00 postoperatively. There were statistically significant differences between the two groups as regard the mean VAS in 1,2,3,4 hours, Fentanyl group had lower median pain score than Control group. Addition of fentanyl to local anaesthetic mixtures fasters the onset and prolongthe duration of akinesia and improve quality of postoperative pain in peribulbar block.

Fentanyl is extensively used for anaesthesia and analgesia in the operatingroom and intensive care unit .It is frequently given intrathecally as a part of spinal anaesthesia or epidurally as a part of epidural anaesthesia and analgesia, it is also used as a sedative. 1 Addition of small amount of localanaestheics augments the effect of intrathecal opioids by increasing the duration of the block and speedingthe onset of analgesia. 2 Fentanylis added commonly to local anaesthetic administrated in the extradural space to improve analgesia in the postoperative period. 3 The addition of fentanyl produced only slight change in the quality and duration ofanalgesia afteradministration of2% lidocaine with epinephrine for a short surgical procedure 4 or after administration of 0.125% bupivacaine 5 , other studies 6 in adults report improved and/or prolonged analgesiafollowing the addition offentanyl tolumbar extraduralbupivacainefor lowerabdominalprocedures,caesarean section and pain relief in labour. 7 This study is designed to examine the effect of adding fentanylto localanaesthetics in peribulbar block on the onset and duration of lid and globe akinesia and postoperative analgesia.

Methods
After institutionalapprovalandinformed consent, 40 adult patients of both sexes with ASA grade 1-2, scheduled for vitrectomy due to vitreous hemorrhage were divided into two groups each of them 20 patients randomly byusing atable ofrandom numbersand sealed closed envelopes in a randomized fashion.
Completeophthalmologicalexaminationwasdone by theophthalmologist aswellasophthalmic ultrasound and biometry was done for all cases to exclude complicated vitreous hemorrhage, diagnosis ofany associated disordersand diagnosis of posterior staphyloma if it was present, also the axial length was measured.
2-Patients havinghistory of abnormal bleeding or allergy to local anaesthetics.
3-Patients with complicated vitreous hemorrhage as retinal detachment, extensive epiretinal membranes, drooped nucleus or IOL, as such surgery takes a long time or when the surgeon expected prolonged surgery (= 2 hrs). 4-Patients with posterior staphyloma. 5-Patients with axial length more than 28 mm.
Aftersecuringintravenousaccess, 1mgmidazolam was given intravenouswith 25mcgfentanyland topical anaesthesia in the form of tetracaine eye drops 0.5 % applied to both groups. 2 mllidocaine 2% diluted with 13 mlsaline to form mixture for painlesslocalinjection 8 . 1 ml from these mixture was given transconjunctival in the medial canthus in the tunnel (between the caruncle and the medial canthalangle) with insulin needle 1 cm length 27G ,then 3-5 mlof localanaesthetic mixtures accordingto each group was injected with needle 27G and 3 cm length with angle 45°between the caruncle and medial canthalangle till the tip of the needle touch theethmoidbone thenthedirectionof theneedle changed to 90°with the hub of the needle at the level of the iris. Other3-5mlfrom localanaesthetic mixturewas injected in the extreme inferotemporal border of the orbit with the same needle 27G and 3cm length directed downward and medially below the globe. Light orbital compression for 1 minute then evaluation after 1minute, 3 min, 5min, and10minute. The appearance of proptosis and chemosiswas observedimmediately afterthe block. The onset and duration of lid and globe akinesia were assessed every 1 minute untilmaximum blockade and then every 15 minutes after surgery untilcomplete recovery of the block.

Evaluation of the block:
Motor blockevaluation includes lid akinesia ( lid closure by orbicularis and lid opening by the levator) and globe akinesia using3 pointscale for every muscle was done usingthe score system that shown in Table 1 For assessment of lid akinesia the patients were asked to open their eyelids and then squeeze them together maximally. Orbicularis occuli muscle was assessed separately by using the score in Table 1. Also levator palpebrae muscle for opening eye lid was assessed by the score in Table 1. Globe akinesia was assessed at1 minute,then 3minute, 5minute, 10 minute and 15 minute. These were scored using the movements of the extraocular muscles in all 4 main directions on a scale of 0 to 2 as shown in Table 1. The blockwas considered satisfactory when loss of at least two movement of the 4cardinal direction. 10 Arterial blood pressure, heart rate and oxygen saturation (SpO2) were checked every 15 minutes duringthe entire procedure and every 30minutes during the first two postoperative hours. Hypotension and bradycardia were defined as a 20% decrease in blood pressure and heart rate in relation to preblock value.
Postoperative analgesia was assessed by using VisualAnalogue Score (VAS) every hour up to 6 hours postoperatively as 0 (no pain) to 10 (maximum pain imaginable). If the VAS was>5, injection of diclofenac 75 mg intramuscular was given. Enquiry was made about any adverse effect suchas nausea,vomiting, dryness of mouth, dizziness, diplopia and blindness.

Statistical analysis of data
Statisticswere doneby computer using Epi-info. Software version 6.04. A word processing, database and statistics program (WHO, 2001).The tests used were: X(mean), SD (standard deviation): to measure the centraltendency of data andthe distribution of data around their mean value. Student's t test: for testing statisticalsignificant difference between mean values of two samples. X 2 test (Chisquare test) to test for statistical significant relation between different variable or grades in qualitative data. ANOVAor F test: to test for significant difference between more than two samples mean values. Mann Whitney test: non parametric test for comparing two groups of data not normally distributed or forsmall sample size. Fisher exact test:for comparingtwo independentproportions whenthe expected observation in any cell of the table is below 5. Significant result is considered if P < 0.05. Highly significant result is considered if P < 0.01.

Results
There was no statistical significant difference between the two groups in the generalcharacteristics including age, sex, weight, volume or in duration of surgery as shown in Table 2. Akinesia of extraocular muscles including the levator muscle. 0 = 0 -1 mm movement in 1 or 2 main directions. or 0 to 4 mm movement in levator muscle. 1 =1 mm movement in more than 2 main directions or 2 mm movement in anymain direction or more than4 mm movement in levator muscle. 2 = > than 2 mm movement in any main direction or 2 mm movement in 2 or more maindirection Akinesia of orbicularis muscle. 0= Complete akinesia.
1= Partial movement in either or both eyelid margins.
2= Normal movement in either or both eyelid margins.  The resultof eyelid closureakinesia wasthe same as result of eye lid openingakinesia and showed statistically significant difference between the two groups in theonset of lid akinesiaat 5min(no patientsin Fentanyl group remained to 5 min while in Control group 3 patients remained and got complete akinesia at 5 min). So fentanylgroup had a statistically significantly faster onset of lid akinesia than control group.  There was statistically significant difference between the two groups in the duration of lid akinesia fentanyl group have prolonged duration of akinesia but faster onset as shown in Table 3.  There was statistically significant difference between the two groups in the onset of globe akinesia at 3,5 min, 3 patients (15%) in Controlgroup got a complete akinesia at 3 min and 14patients(70%) at 5 min; while in Fentanyl group 13 patients (65%) and 6 patients (30%) respectively.  There wasstatistically significant differences between the two groups in the duration of globe akinesia Fentanylgroup have long durationin akinesia but faster onset (Table 4). ticallysignificant differences in peripheraloxygen saturation, heart rate and non invasive blood pressure between the two groups. Statisticallysignificant *P value< 0.05 highly significant ** P value <0.001  There was highly significant difference between the two groups in first time to require analgesia. In the first hour 30 % of patients (n=6) required analgesia and 55 % (n=11) in the second hour but no patients required analgesia in Fentanylgroup but 75% (n=15) patients in Fentanyl group required analgesia after 3 hours (Table 5).  There was statistically significant differences between the two groups as regard the median VAS at 1, 2, 3, 4, 5, 6 hours Fentanyl group had lower median pain score than Control group. Postoperative analgesia given in both groups when VAS >5 (Table 6).
 We did not observe any side effect during the study related to peribulbar block, there were no statis-

Discussion
Opiates are widely known to have an antinociceptive effect at the central and/or spinal cord level 11. However,evidence has begun toaccumulate that opioid antinociception can be initiated by activation of peripheral opioid receptors 12. The presence of peripheralopioid receptors is shown in immune cells and primary afferent neurons in animals. 13 If opioid administration improves regional anaesthesiawithout centrally mediated side effects, it would beuseful in clinical practice.
Study has demonstrated the presence of peripheral opioid receptors that mediate analgesia by endogenous as wellas exogenousopioid agonists. 14 It isspeculated that the peripheraladministration of opioids provide stronger and longer lastinganalgesia with a lower dose of opioid without central side effects such as res-piratory depression, nausea, vomiting and pruritus. 15 A number of trials have examined the peripheral analgesic effect of opioids in a large variety of surgical settings particularly arthroscopy and conduction nerve blocks. 16,17 Theaddition ofopioids in brachialplexus block is reported to improve success rate and postoperative analgesia. 18 We postulate the possible mechanisms of action for the improvedanalgesia produced by the peripheral applicationof fentanyl.First, fentanyl couldact directly on the peripheralopioid receptor. Primary afferent tissues (dorsal roots) have been foundto contain opioid binding sites 13 . Because the presence of bidirectional axonaltransport ofopioid bindingprotein has been shown 19 fentanyl may penetrate the nerve membrane and act at the dorsal horn. This could also account for the prolonged analgesia. However, fentanylis reported to have a local anaestheticaction. 20 Gormley et al 18 suggested that alfentanil also prolonged postoperative analgesia by localanaesthetic action.
Second, fentanylmay potentiatelocal anaesthetic action via central opioid receptor-mediated analgesia by peripheraluptake offentanyltosystemic circulation. 21 Whether fentanyl diffuses from the peribulbar space to the subarachnoid space around theoptic nerve in the reterobulbar space or not to clarify this issue, the spinalfluid fentanylconcentrationsshouldbe measured.
A synergisticinteraction betweenlocalanaesthetics and opioidswith epiduraladministration has been reported. 22 It appears that local anaesthetics and opioids exert theiraction independentlyviadifferent mechanisms. Local anaesthetics block propagation and generation of neural action potentials by a selective effect on sodium channels, whereas opioids act on the opioid receptorscreatingan increasein apotassium conductance. This actionresults in hyperpolarization of the nerve cell membrane and a decrease in excitability 23 . Although sodium channel blockis proposed to be the primary mode of action, local anaestheticsalso have an effect on synaptic transmission 24 . Li et al 24 showed that lidocaine inhibited both substances P bindingandsub-stance P-evoked increase in intracellular calcium. In contrast, in addition to the considered primary mode of action, opioids were found to directly suppress the action potentialin nerve fibers 25 . Frazier et al 26 showed that morphinedepressed both sodium and potassium currents associated with the action potentialin squid giant axons. Therefore, the combination of local anaestheticsand opioids may effectivelyinhibit multiple areas of neuronal excitability.
Theaddition of hyaluronidase to local anaesthetic mixtures decreases the onset time of peribulbar block and quality of akinesia in most reported studies. 27 The present study compares the effect of additionof fentanylto localanaesthetic mixturesinperibulbar blockon the onset and duration of complete akinesia. The results of the present study showed that addition of fentanyl to local anaesthetic mixtures in peribulbar block fasten the onset of block ( 80% of patients get complete lid akinesia at3 minand nopatients remained to 5 min while in control group15% get complete lid akinesia at 5 min and 5% at 10 min.). Also Fentanyl group had a short onset in globe akinesia 65% at 3 min , 30% at 5 min and only 5% at 10 min but in Control group 15% at 3 min, 70% at 5 min and 15% at 10 min. As regard duration of lid and globe akinesia Fentanyl group had longer duration than control group. The results of the present study are in accordance with study done by Toshiharu et al 28 who studied the effect of addition of fentanylto mepivacainein epiduralblock and found that addition of fentanyl to mepivacaine accelerate the onset of analgesia and enhances the analgesic effect of epidural block. Deniz et al 29 found that addition of fentanylto bupivacaine in brachial plexus axillary approach prolonganaesthesia and analgesia, prolongduration of sensory and motor blockand prolong the duration of postoperative analgesia. In the present study the first time to require analgesia is prolonged in Fentanylgroup, in which 75% of patients required rescue analgesia 3 hour postoperative while in Control group 30% required it in first hour and 55% in second hour and 15% in the third hour .These results are similar to the results of constant O et al 30 who studied the effect of addition fentanylto local anaesthetic mixture in caudal block in children undergoing bilateral vesicoureteral reflex and they found that addition of fentanyl (1 mcg.kg -1 ) to bupivacaine 0.25% and lidocaine 1% prolong duration of surgical analgesia after single injection from start of injection to first requirement of analgesia from 174min in Control group to 253min in Fentanylgroup. In the present study fentanyl group had lower pain score postoperatively than in Control group. In accordance with the study done by Vita et al 31 who found that intraarticular injection of fentanylimprove postoperative pain and no difference between intraarticular morphine and fentanyl in postoperative pain relief.
Also Vijay et al 32 foundthat wound infiltration with fentanylhas lower VAS postoperativelyand combination of lidocaine with fentanylfor wound infiltration in cholecystectomy patients was associated with better postoperative analgesia, reduced analgesic consumption and better lung function. Saryazdiet al 33 foundthat injection of fentanylintraarticularly has better postoperativepain less pain score and short time to walk were achieved by fentanyl or pethedine in comparison with dexamethasone wheninjected intraarticular.